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Good Clinical Practice:

Good Clinical Practice 4 A Set of Responsibilities ‘a process that makes all parties to a study responsible for patient safety and study quality ’

What is GCP ?:

What is GCP ? Good Clinical Practice (GCP) is defined as a ‘standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity and confidentiality of trial subjects are protected’ 5

GCP:

GCP Are mainly focused on the protection of human rights in clinical trial. Provide assurance of the safety of the newly developed compounds. Provide standards on how clinical trials should be conducted. Define the roles and responsibilities of - Clinical Sponsors, Clinical Research Investigators, Clinical Research Associates, And Monitors. 6

The Objectives of Clinical Research:

The Objectives of Clinical Research To Contribute to Public Health To Contribute to Health Science To Contribute to Economic Development 7

US & EU Objectives in Harmonizing GCP (3 August 2009, Launch of a Bilateral GCP Initiative):

US & EU Objectives in Harmonizing GCP (3 August 2009, Launch of a Bilateral GCP Initiative) 8 To achieve common understandings and practices To share standards and methodologies To share knowledge To share resources To improve human subjects protections

Challenges to GCP Harmonization:

Challenges to GCP Harmonization 9 The extensive reach of clinical trials The complexity of law and regulation Lack of an internationally agreed code of ethics for human research protections The progress of medical science The lack of appropriately representative platforms

Historical perspective:

Tuskegee Experiment :

Tuskegee Experiment From 1932 -1970 with approval from the US Department of Public Health. Poor black men with syphilis were regularly examined and the progress of their disease documented. The “subjects "believed they were receiving optimal medical treatment. The reality was that either inadequate or no treatment at all was being given. As a direct result of this study at least 40 men lost their lives 12

Sulphanilamide disaster 1938:

Sulphanilamide disaster 1938 Sulphanilamide widely available and useful antibiotic Manufacturer dissolved the compound in diethylene glycol to make it in elixir. Following acceptable testing for flavour , appearance and fragrance it was distributed. But toxicity profile was not done 1938 –107 deaths (primarily children) directly attributable to the elixir sulphanilamide 13

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Thalidomide Tragedy 1950/60s:

Thalidomide Tragedy 1950/60s Compound prescribed for nausea in pregnancy throughout Europe No teratogenic testing performed in appropriate animal models Early reports of patients suffering from peripheral neuritis were largely ignored 15

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Estimated 10,000 phocomelics born Despite the evidence the drug manufacturers fought to keep the compound on the market. 16

History of Good Clinical Practice:

History of Good Clinical Practice Prior to an actual set of guidelines to follow for good clinical practice, clinical studies were dangerous and could result in serous disease, or possibly death. The Nuremburg Code of 1947 Experiments performed in Germany during WWII opened the eyes of the world for guidance for clinical testing on humans. The code did set ethical guidelines, but it lacked legislation to back it up. Declaration of Helsinki In 1964, the World Medical Association established recommendations guiding medical doctors in biomedical research involving human subjects. These guidelines influenced national legislation, but there was no set standard between nations. 17

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Glossary:

13 Principles of ICH GCP:

13 Principles of ICH GCP Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirements. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject & society . A trial should be initiated and continued only if the anticipated benefits justify the risks. Benefits RISKS 20

13 Principles of ICH GCP Continued:

13 Principles of ICH GCP Continued The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science & society. The available non-clinical & clinical information on an investigational product should be adequate to support the proposed clinical trial. Clinical trials should be scientifically sound, and describe in a clear, detailed protocol. A trial should be conducted in compliance with the protocol that has received prior IRB (or IEC) approval. 21

13 Principles of ICH GCP Continued:

13 Principles of ICH GCP Continued The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist. Each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective tasks. Freely given informed consent should be obtained from every subject prior to clinical trial participation. 22

13 Principles of ICH GCP Continued:

13 Principles of ICH GCP Continued All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification. The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory compliance. 23

13 Principles of ICH GCP Continued:

13 Principles of ICH GCP Continued 12. Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol 13. Systems with procedures that assure the quality of every aspects of the trial should be implemented. 24

Institutional Review Board (IRB), Independent Ethics Committee (IEC):

Institutional Review Board (IRB), Independent Ethics Committee (IEC) A formally designated group that oversees research involving human subjects. Approves and disapproves human subject research. According to the standards of the community or the institution, the IRB/IEC may require modifications to a protocol to ensure patient safety. 25

IRB Function :

IRB Function • The primary function of an IRB/IEC is to safe guard the rights ,safety ,and well being of all trial subjects . This is accomplished by initial, continuing and annual review. •An IRB should consist of members who collectively have the qualifications and experience to review and evaluate the science , medical aspects, and ethics of the proposed trial. 26

IRB Members :

IRB Members 1. A minimum of five (5) members. 2. One member whose concern is not scientific. 3. One member who has no personal or familial relationship to the institution or trial site. 4. Any member with a conflict of interest may not participate in any part of the review or vote (except to provide requested information). 5. Individuals with special expertise may be invited to assist with areas of unique or complex nature. These will not be voting members. 6. A list of IRB/IEC members and their qualifications should be maintained. 27

IRB/Ethics Committee:

IRB/Ethics Committee All studies must be approved prior to recruiting participants IRB must review all documents given to participants Reporting AEs and Deviations from protocol to the IRB Maintenance of Records 28

Investigator Responsibilities:

Investigator Responsibilities Compliance with Protocol Investigator should sign off on protocol Investigator should not implement deviations from protocol If deviations occur, they should be documented and reported at once to the sponsor, the IRB and other regulatory authorities 31

Investigator Responsibilities:

Investigator Responsibilities Progress Reports Written summary of trial status to the IRB Written reports to the sponsor or regulatory authority of any changes affecting the trial Safety Monitoring SAEs should be reported immediately to sponsor AEs should be reported according to sponsor guidelines Supply sponsor & IRB with requested materials on participant deaths 32